Cancer is one of the major causes of death in humans and animals. Millions of people in the world are diagnosed every year as having cancer and a large proportion of these people die of cancer. Despite extensive worldwide effort over many years, cancers continue to be hard-to-treat diseases, and there is an urgent need for more effective anticancer drugs.
Dithiolopyrrolones are a group of compounds with 1,2-dithiolo[4,3-b]pyrrol-5(4H)-one ring. The substitutes attached to the ring, particularly at position 2 and 6, lead to diverse subgroups of derivatives with different structural features and bioactivities. Compounds bearing this basic structural feature have been known in the art. Natural dithiolopyrrolones have been shown to have activities against micro-organisms as well as other activities such as chemopreventive (Sharma et al., 1994) and anticancer (U.S. Pat. No. 6,020,360, WO 99/12543 both of Webster et. al.). Certain synthetic dithiolopyrrolones and their antimicrobial activities have been disclosed (D. S. Bhate & Y. M. Sambray, 1963. Hindustan, Antibiotic Bulletin 6(1): 17-18; Katsuaki Hagio et al. Bull. Chem. Soc. Jpn 1974, 47, 1484-1489; Broom, et al. WO 9505384 and Godfrey & Dell, GB2170498).
The present invention relates to certain new types of dithiolopyrrolones and particular specific dithiolopyrrolones that have been found to have particular use in the treatment of cancers. The invention relates to such types and particular compounds as new chemical compounds, and also to pharmaceutical compositions containing them and methods for the treatment of disease using them.
In addition, and more generally, such types of dithiolopyrrolones and particular specific dithiolopyrrolones are found to be useful against proliferative diseases in general. Proliferative diseases are, but are not limited to, disorders wherein unwanted cell proliferation of one or more subset(s) of cells in a multicellular organism occurs, resulting in harm (e.g., discomfort or decreased life expectancy) to the multicellular organism. Proliferative diseases can occur in different types of animals and in humans. Proliferative diseases include leukemia and blood vessel proliferative disorders, and fibrotic disorders such as cancers, tumors, hyperplasias, fibrosis (especially pulmonary fibrosis, but also other kinds of fibrosis, such as renal fibrosis), angiogenesis, psoriasis, arteriosclerosis and smooth muscle cell proliferation in the blood vessels, such as stenosis or restenosis following angioplasty.